Frequency of caucasian hemochromatosis-associated tyr250stop (y250x) mutation in the non-classicaf, transferred receptor gene tfr2 in african americans

Academic Article


  • Primary iron overload is common in sub-Saharan African natives and has been reported in African Americans. This disorder is not linked to HLA loci on Chop, and inheritance of two Caucasian hemochromatosis-associated missense mutations of the HFE gene c n Chop has not been described in affected persons. Some African Americans with ire n overload are simple hétérozygotes for the common HFE missense mutations C282Y ar d H63D. The uncommon hemochromatosis-associated missense HFE alleles S65C, HOST, and G93R have not been detected in African Americans with iron overload (J.C. Barto i, personal communication). Camaschella et al. recently discovered a stop-codon mutatic n ( Y250X) of the TFR2 gene (Ch7q22) in two unrelated Sicilian families with HFE mutatioi inegative hemochromatosis (Nat Genet 2000;25:14-5), and suggested that Y250X migit also be associated with African iron overload. In addition, the non-classical transferr n receptor TfR2 in mice appears to permit continued uptake of transfetrin-bound iron t y hepatocytes after down-regulation of the classical transferrin receptor TfR by iron overload (Fleming et al, Proc Natl Acad Sei USA 2000;29:2214-9). Thus we assessed the frequency of Y250X in 287 African Americans who reside in central Alabama (172 unrelated normal controls, 100 women with non-insulin-dependent diabetes mellitus, and 15 index cases Jrf primary iron overload). We used our "sequence-specific priming" PCR reaction modification of the original PCR-RFLP assay; our technique does not require restriction endonuclease digestion and can be performed on DNA from buccal swabs. The Y250k mutation was not detected in any of the 287 African Americans. We conclude that: 1) the allele frequency of TFR2 Y250X is < 0.003 among our African American normal control subjects; and 2) Y250X does not occur commonly in association with non-insuli|dependent diabetes mellitus or primary iron overload in African Americans in central Alabama.
  • Authors

    Published In

  • Blood  Journal
  • Author List

  • West PA; Rivers CA; Barton EH; Barton JC; Acton RT
  • Volume

  • 96
  • Issue

  • 11 PART I